dbSNP rs998707315: TBC1D24:c.-116+3G>C (chr16-2475173-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199107.2(TBC1D24):c.-116+3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Consequence

TBC1D24
NM_001199107.2 splice_region, intron

Scores

Splicing: ADA: 0.2275

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

Variant links:

Genes affected

TBC1D24 (HGNC:29203): (TBC1 domain family member 24) This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

TBC1D24 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBC1D24	NM_001199107.2 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 7	ENST00000646147.1	NP_001186036.1	Q9ULP9-1
TBC1D24	NM_020705.3 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 6		NP_065756.1	Q9ULP9-2
TBC1D24	XM_017023493.2 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 8		XP_016878982.1	Q9ULP9-1
TBC1D24	XM_017023495.2 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 7		XP_016878984.1	Q9ULP9-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D24	ENST00000646147.1 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 7		NM_001199107.2	ENSP00000494678.1	Q9ULP9-1
TBC1D24	ENST00000567020.6 link	c.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 6	1		ENSP00000454408.1	Q9ULP9-2
TBC1D24	ENST00000569874.2 link	n.-116+3G>C	splice_region_variant, intron_variant	Intron 1 of 7	5		ENSP00000455005.2	Q9ULP9-2
TBC1D24	ENST00000630263.2 link	n.-142+3G>C	splice_region_variant, intron_variant	Intron 1 of 7	5		ENSP00000486835.1	A0A0D9SFR5

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000670

AC:

AN:

149204

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72702

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.23

dbscSNV1_RF

Benign

0.55

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over